Kaplan M D, Taylor S E, Ambudkar I S
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Pflugers Arch. 1994 Oct;428(5-6):439-45. doi: 10.1007/BF00374563.
In the human submandibular ductal cell line (HSG) thapsigargin and carbachol stimulated Ca2+ release from the internal Ca2+ pool, resulting in the activation of capacitatively regulated Ca2+ entry (CRCE). This entry pathway was permeant to both Ca2+ and Mn2+, blocked by Ni2+ and insensitive to the muscarinic antagonist, atropine. Carbachol also stimulated an increase in cytosolic [Ca2+] in internal Ca(2+)-pool-depleted (i.e. thapsigargin-treated) cells which was dependent on the presence of external Ca2+ and blocked by Ni2+, demonstrating that it was due to Ca2+ entry. However, under the same experimental conditions, carbachol was unable to stimulate Mn2+ entry. Additionally, this latter carbachol-stimulated Ca2+ entry pathway was blocked by atropine. Pretreatment of HSG cells with AlF4-increased basal rates of Mn2+ entry due to CRCE activation, but attenuated carbachol-stimulated Ca2+ entry into thapsigargin-treated cells. The data suggest that two distinct divalent cation entry pathways are activated in muscarinic-receptor-stimulated HSG cells; a CRCE mechanism, permeable to both Mn2+ and Ca2+, and a second entry mechanism, permeable only to Ca2+. The latter does not depend on internal pool depletion, but appears to be regulated via G-protein activation.
